Apparatus and method for measuring components in a bag

ABSTRACT

An apparatus for measuring components in a liquid medium, in particular parenteral nutrients, within a flexible transparent bag. A spacer is utilized to fix or determine the optical path across the bag chamber and includes a passage for electromagnetic radiation of selected wavelengths. The source of electromagnetic radiation is capable of sending radiation into the bag chamber and to detector means which analyzes the radiation passed through or reflected from the components in the bag chamber.

BACKGROUND OF THE INVENTION

The present invention relates to a novel and useful apparatus and methodfor non-invasively analyzing liquid medium components in a bag.

Liquid compounds are often placed in bags for various purposes. Forexample, the use of total parenteral nutrients (TPN), which areeventually the source of intravenous feeding, are stored in transparentor translucent flexible bags. TPN compounds are commonly mixed inpharmacies using commercially available compounders which accept threeor more TPN compounds and automatically mix these compounds into anappropriate container such as an intravenous (I.V.) bag. Intravenous useof the bags usually takes place at a later time in a hospital or medicalfacility. Typical compounds include 70% dextrose injection U.S.P., 10%Travasol (amino acid) injection, Intralipid 20% fat I.V. emulsion,sterile water, and many others.

Presently, methods such as color coding are relied upon to avoid makingerrors during the compounding or mixing process. Namely, different tubesfeeding the I.V. bag possess connectors of different colors whichcorrespond to the colors of the specific mixing positions on thecompounder. For example, setting a red indicator on a compounder for 100milliliters would deliver 100 milliliters from a starting bottleconnected to the tubing line which possesses red connectors. However,there is no assurance that the correct compound was initially connectedto the red tubing line. Consequently, an incorrect connection of thetubing between bottles of dextrose solution and water, for example, mayhave dire consequences, such as death for patients with sugarintolerance.

Many of the TPN compounds are clear liquids. That is to say, water,amino acid injection, dextrose injection, and electrolytes are clearliquids precluding visual distinction among them. Furthermore, it ispreferable to perform identification of TPN components non-invasivelyand rapidly to minimize potential contamination and to minimize analysistime by personnel.

An article entitled "Near Infrared Multi-Component Analysis ofParenteral Products Using the InfraAlyzer 400," by Rose et al. examinedmeglumine and meglumine diatrizoate in 30% diatrizoate meglumineinjections solutions using diffuse reflectance in the near infraredregion. The best combinations of three or four wavelength filters fromnineteen (19) available wavelength filters were selected using multipleregression statistical methods. The specific wavelengths were notidentified.

An article entitled "The Spectrophotometric Absorbance Of Absorbance ofIntralipid" by Carne et al. develops calibrations for Intralipid inwater in concentrations from 2.5 to 40 mg/ml at six (6) visiblewavelengths between 505 and 626.6 nanometers. Intralipid interferes withspectrophotometric analysis of oxyhemoglobin, carboxyhemoglobin, andtotal hemoglobin.

A writing entitled, Simple Methods For Quantitative Determination ofProcaine Hydrochloride In Parenteral Products by Das Gupta et al.presents calibrations in the ultraviolet region of spectrophotometry.Specifically, the Das Gupta reference obtained calibrations at 228nanometers for buffered solutions of procaine hydrochloride in the 0-20microgram/ml concentration range.

An article entitled "Nondestructive NIR and NIT Determination OfProtein, Fat, And Water In Plastic-Wrapped, Homogenized Meat" byIsaksson et al., describes NIR measurements of proteins by diffusereflectance in meat samples with and without plastic coatings. Sampleswere placed in a rubber cup prior to covering the meat sample withplastic laminant.

U.S. Pat. Nos. 4,800,279 and 5,002,397 describe methods and devices forvisible and near-infrared evaluation of physical properties of samples.

U.S. Pat. No. 4,872,868 shows an analyzer for collection bags whichprovides an envelope that permits the insertion of reagent's test stripsand the like.

U.S. Pat. Nos. 3,857,485 and 3,924,128 teach a method of analyzingsample containers by liquid scintillation spectrometry which utilizeslight transmission sealing means to prevent entry of ambient light orthe escape of light from the photomultiplier tube detection devices.

U.S. Pat. No. 5,239,860 describes a sensor for continuously measuringalcohol and gasoline fuel mixtures in a clear Teflon tube using apre-determined optical path and electromagnetic radiation at a pair ofwavelengths which are generated by rapidly switching currents through alight-source. Thermopile detectors are used to detect an increase intemperature due to light transmitted through the flowinggasoline/alcohol mixture.

An apparatus and method for identifying solutions in a translucenttransparent or semi-transparent plastic bag, such as parenteralnutrients, non-invasively, qualitatively and quantitatively would be anotable advance in the chemical analysis field.

SUMMARY OF THE INVENTION

In accordance with the present invention a novel and useful apparatusand method for identifying parenteral nutrients is herein provided.

The apparatus of the present invention employs spacer means forsupporting a flexible transparent or translucent bag and for determiningthe optical patch across the bag chamber. The spacer means includes apassage for electromagnetic radiation. The spacer means may take theform of a pair of rigid elements or fences and a mechanism forshortening or lengthening the distance between the rigid fences. Therigid fences may support the bag against vertical movement and also becapable of exerting compressive force on the bag to a preciselydetermined dimension between the rigid fences. Such dimension wouldcorrespond to a particular optical path, which may include the bag wallalone or the bag wall and the bag filled with components in a liquidmedium.

A source of electromagnetic radiation directs electromagnetic radiationthrough the spacer passage and to the wall portion of the bag. Thesource of electromagnetic radiation may produce coherent light,ultraviolet radiation, x-rays, infrared radiation, broad band radiatione.g., a tungsten source, and the like.

Detector means is also employed in the present invention for analyzingthe electromagnetic radiation passed through the spacer passage andalong a determined optical path which is through a dimension of the bagchamber. In certain cases the optical path may pass completely acrossthe bag such that the detector is receiving light which has beentransmitted through the bag. In other cases, the detector may be placedon the same side of the bag as the source of electromagnetic radiationand receive light which has interacted with the contents of the bag bydiffuse reflectance. Further, the detector may receive light by diffusereflectance and/or by diffuse transflectance, i.e., where light passesthrough the bag and then is reflected back through the bag by a diffusereflector or mirror located on the opposite side of the bag relative tothe detector. It has been found that near-infrared radiation isparticularly useful in detecting parenteral nutrients in a flexible I.V.bag. In addition, specific wavelengths, rather than a continuum ofwavelengths, may be used as the radiation sought for analysis to enablethe use of simpler and less expensive instrumentation comprised ofseveral discrete detectors, each covered by a narrow wavelength filter.Fiber optics may also be utilized to carry light to and from the I.V.bag. Mathematical models may be employed to quantitatively andqualitatively detect components within the I.V. bag accurately andquickly.

Another adaption of the device of the present invention produces a selfreferencing device with respect to the intensity. Specifically,transmittance measurements may be taken of the bag alone, squeezed toeliminate a chamber and to expel the liquid components, and along adetermined optical path of the bag filled with certain components.Absorbance for a sample may be accurately determined under the Beer'sLaw relationship. Chemical concentration can be directly related to anabsorbance difference obtained from a spectral measurement using twodifferent path lengths. This technique minimizes or eliminates commonspectroscopic measurement problems due to contamination, changes in thespectroscopic windows holding the sample, instrument problems due totemperature changes on internal optical elements, the source ofelectromagnetic radiation, and the like.

It may be apparent that a novel and useful apparatus for analyzingcomponents in a liquid medium has been described.

It is therefore an object of the present invention to provide anapparatus and method for analyzing liquid components in a flexibletransparent or translucent container or without invading the integrityof the bag.

Another object of the present invention is to provide a method andapparatus for analyzing components in a liquid medium within a flexibletransparent or translucent container to prevent misuse of suchcomponents in treating patients in a medical facility.

A further object of the present invention is to provide a method andapparatus for analyzing components in a liquid medium found in atransparent or translucent plastic container which is accurate and mayinclude qualitative as well as quantitative measurements of thecomponents therein.

A further object of the present invention is to provide a method andapparatus for analyzing components in a liquid medium found in atransparent or translucent flexible bag where such components areparenteral or enteral nutrients typically used for intravenous feeding.

A further object of the present invention is to provide a method andapparatus for analyzing components in a liquid medium found in atranslucent flexible bag which is capable of detecting light from asource after interaction with the bag alone and after interaction withthe bag and the components in the bag.

Another object of the present invention is to provide a method andapparatus for analyzing components in a liquid medium within a flexiblebag employing either transmittance or diffuse reflectance techniques.

The invention possesses other objects and advantages especially asconcerns particular characteristics and features thereof which willbecome apparent as the specification continues.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a sectional view of a first embodiment of the apparatus of thepresent invention.

FIG. 2 is a sectional view of the apparatus of FIG. 1 taken along line2--2 of FIG. 1.

FIG. 2A is a sectional view taken along line 2A--2A of FIG. 2.

FIG. 2B is a sectional view of an I.V. bag collapsed by the apparatus ofthe present invention.

FIG. 3 is a side sectional view of another embodiment of the apparatusof the present invention.

FIG. 4 is a graphical representation with experimental results describedin Example 1.

FIG. 5 is a graphical representation of the experimental resultsdescribed in Example 2.

FIG. 6 is a graphical representation of experimental results describedin Example 3.

FIG. 7 is a graphical representation of an experimental result describedin Example 4.

FIG. 8 is a graphical representation of PCA plot of scores described inExample 5.

FIGS. 9 and 10 are graphical representations depicting predictions usingPLS analysis described in Example 4.

FIG. 11 is a graphical representation of a PLS model utilizing datafound in Example 4.

FIGS. 12, 13, and 14, are graphical representations of MLR methodsapplied to the data shown in Table 2 of Example 4.

FIG. 15 is a graphical representation of a step wise MLR programutilizing the data of Table 1 of Example 4.

For a better understanding of the invention reference is made to thefollowing detailed description of the preferred embodiments which shouldbe referenced to the herein before described drawings.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Various aspects of the present invention will evolve from the followingdetailed description of the preferred embodiments thereof which shouldbe taken in conjunction with the hereinbefore described drawings.

The invention as a whole is depicted in the drawings by referencecharacter 10. The apparatus 10 is shown in the drawings as includingmultiple embodiments, denoted by the addition of an upper case letter.Referring to FIG. 1, apparatus 10A is depicted in which spacer means 12is provided to hold a flexible transparent or semi transparent bag 14 inplace. The term "translucent" is used herein to indicate a transparent,semi-transparent, or non-opaque bag. Bag 14 includes a chamber 16 whichis capable of holding components in a liquid medium 18. Liquid mediumincluding such components 18 are passed through tube 20, shown partiallyin FIG. 1, which is ultimately clamped or sealed when the bag 14 isfilled. Bag 14 may take the form of a plastic intravenous bag (I.V. bag)formed of polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), andlike materials. However, other containers may be employed herein. Theliquid medium and components 18 found within bag 14 may consist ofmixtures of parenteral or enteral nutrients which may be intravenouslyfed to a patient. For example, such nutrients may include sterile water,70% dextrose injection U.S.P., 10% Travasol (amino acid) Aminosyn orFreeAmine injection, Intralipid 20% fat I.V. emulsion, potassiumchloride, and the like, individually or in various combinations.

Spacer means 12 includes a pair of elements 22 and 24 which are shown inFIGS. 1 and 2 as a pair of solid fences placed in opposition to oneanother. Fences 22 and 24 are slidingly supported by rods 26 and 28which are supported to a surface by stands 30 and 32, depicted inphantom on FIGS. 1 and 2. Rods 26 and 28 serve as a guide for fences 22and 24. A threaded screw 34 is fixed to fence 22 through a boss 36.Knurled wheel and bearing unit 38 is capable of turning relative to boss36. The turning of wheel 38 also rotates threaded connect screw 34 whichthreadingly engages a threaded bore 40 through fence 24. Thus, fence 22is stationary relative to rods 26 and 28 while fence 24 is moveablethereto, manually or by motor means, such as a solenoid, directionalarrow 25. Unit 38 serves to measure or to stop the relative movement offences 22 and 24, to determine the optical path through bag 14 orsequentially determine a plurality of optical paths through bag 14. Itshould be noted that fences 22 and 24 may be hingedly attached to oneanother to determine the distance therebetween, like a clamshell.

With reference to FIG. 2A, it maybe observed that such optical path(O.P.) of components 18 within bag 14 may be easily adjusted by themovement of fence 24 relative to fence 22. The O.P. may vary between 1.0millimeter to 15 millimeters in many cases. In certain instances, anempty bag 14 may be compressed by fences 22 and 24 such that walls 42and 44 touch one another, FIG. 2B, eliminating chamber 16. Thisconfiguration is useful in obtaining a reference value for the bagwithout medium 18 in chamber 16. Inner surfaces 42 and 44 of fences 22and 24, respectively also provide sufficient friction to prevent theslippage of bag 14 downwardly between fences 22 and 24. Of course, otherstructures may be employed to prevent the slippage of bag 14 withinspacer means 12 such as a floor, or suspension device pulling upwardlyon bag 14 while bag 14 is within spacer means 12, and the like.

Apparatus 10 further possesses a source of electromagnetic radiation 46.Source 46 may take the form of laser light, infrared radiation,ultraviolet radiation, visible radiation, or any other electromagneticradiation found in the spectrum. Light 46 is passed to bag chamber 16through passage 48 in fence 22 and from chamber 16 of bag 14 throughpassage 50 of fence 24. Electromagnetic radiation from source 46 may befiltered by filter 52 and led to passage way 48 by optical fiber orfiber bundle 54. Fitting 56 directs radiation from fiber optical bundle54 to collimating lens 58. Parallel rays of electromagnetic radiationare then passed through bag 14 and liquid medium 18 containing variouscomponents to converging lens 60. Fitting 62 directs the electromagneticradiation through optical fiber or fiber optic bundle 64 to a detector66 for analysis. Detector means 66 in its broadest sense may take theform of any suitable spectrophotometer, single or multiple detectors, orsources being appropriately filtered for the wavelength of interest, incombination with a computer employing an appropriate software programsuch as Gram 386, available from Galactic Industries, Inc. of Salem N.H.

With reference to FIG. 3, embodiment 10B of the present invention isdepicted. Apparatus 10B possesses a pair of opposing elements or fences68 and 70. As in embodiment 10A, guide 72 may take the form of a pair ofrods supported by stands on a surface, a hinged clamshell configuration,or the like. Fence 68 is fixed to guide 72 while fence 70 is moved andthe distance between fences 68 and 70 is set by threaded screws 74, inthe same manner as threaded screw 34 found in embodiment 10A. Fence 68includes a diffuse reflector 76 on one side of bag 14 containing liquidmedium 18 having various components therewithin. Of course, diffusereflector may be formed integrally with bag 14. Diffuse reflector 76 maytake the form of a white ceramic disk or other suitable reflector. Lightfrom source 46, not shown, passes through outer fiber or fiber bundle78, from bag 14 containing a liquid medium having various components 18,and through fiber optic bundle 80, which is formed concentrically withfiber optic bundle 78. Analysis of the components within bag chamber 16takes place by interaction of the electromagnetic radiation from fiberoptic bundle 78 by diffuse reflectance, by diffuse transflectance, inconjunction with diffuse reflector 76, or a combination of both. Thelatter is especially useful where liquid medium is murky to an uncertaindegree. Such diffuse reflectance measurements may be obtained simply bypressing an I.V. bag filled with light scattering material against fence70 without the use of fence 68. Again, fiber optic bundles 78 and 80 maybe angularly disposed with respect to each other i.e., 30 degrees, tominimize specular components of electromagnetic radiation reflected frombag 14.

The general operation of embodiments 10A and 10B takes place bysupporting bag 14 within spacer means 12, which may include elements 22and 24 of embodiment 10A, or fences 68 and 70 of embodiment 10B. Spacermeans 12 is then adjusted to solely determine the desired optical pathwithin bag 14 or to sequentially determine the optical path through aplurality of bags such as bag 14. In general, where liquid medium 18 isnot perfectly clear, as in the case of lipids, the optical path would beshort. For murky light scattering liquids, it is unlikely that radiationwill reach the far side of bag 14 and be reflected back from diffusereflector or mirror 76. In such a case, the space between fences 68 and70 is not critical. The converse is true with clear liquid medium 18.Electromagnetic radiation from source 46 is then directed throughpassages 48 and 50 of elements 22 and 24, or simply directed throughpassage 82 of fence 70 of embodiment 10B. After interaction with thecomponents in a liquid medium 18, electromagnetic radiation is passedfrom bag 14 to detector 66 for analysis by a suitable software programin conjunction with a personal computer. Where bag 14 is collapsed byfences 22 and 24, electromagnetic radiation may be passed through bag 14to obtain a reference reading for use with spectral analyses of liquidin bag 14.

This spectroscopic method and apparatus of the present invention iscapable of identifying and measuring many components in a liquid medium18. Colorless materials, such as parenteral nutrients have distinctivespectral characteristics in regions outside the visible electromagneticspectrum (400-700 nm). In particular, infrared (3000-25,000 nm) regionsof the electromagnetic spectrum produces distinctive spectral featuresarising from specific molecular structures that are characteristics ofthe compounds. Such features derive from molecular vibrations of bondedatoms such as oxygen-hydrogen, carbon-hydrogen, nitrogen-hydrogen, andoxygen-carbon. Different types of carbon-hydrogen bonds can bedistinguished, such as those arising from terminal C--H groups or CH₃groups, i.e., fundamental molecular vibrations. Similar features occurat multiples of these fundamental frequencies (i.e., shorterwavelengths) and, hence, commonly occurred in the near-infrared. Theseare referred to as vibrational overtones such as the first and secondovertones of carbon-hydrogen near 1700 and 1100 nm, respectively.Several different fundamental vibrations can combine to form avibrational absorption at shorter wavelengths called a combination mode,ie., such as oxygen and hydrogen in molecular water near 1900 nm.Therefore, many regions of the electromagnetic spectrum may be used toobtain useful spectral data.

While in the foregoing, embodiments of the present invention have beenset forth in considerable detail for the purposes of making a completedisclosure of the invention, it may be apparent to those of skill in theart that numerous changes may be made in such detail without departingfrom the spirit and principles of the invention. Further description ofthe invention is contained in the following examples.

The following examples are described in detail herein for the purpose ofillustration of the present invention, but are not deemed to limit thescope of the invention herein.

EXAMPLE 1

The near infrared spectra of several parental nutrient compounds, i.e.,water, 70% dextrose injection USP and 10% Travasol amino acid injectionwas measured individually or in various combinations to illustratespectral characteristics. Such compounds formed an optically clearsolution, which was placed in a fused quartz cuvette having an opticalpath of one (1) millimeter. The spectral data were acquired with agermanium detector found in a spectrophotometer, Model 200, manufacturedby Guided Wave, Inc. of El Dorado Hills, Calif. Two (2) one meter long,500 micron core diameter, silica-clad low-OH optical fibers andcollimating lenses were connected to the spectrophotometer. Collimatinglenses were placed between one end of each fiber and the cuvette. Onefiber transmitted light from the tungsten light source inside thespectrophotometer through collimating lens and cuvette. The secondcollimating lens received light passing through the cuvette and focusedthe light into the second fiber, which transmitted the light back to themonochrometer and detector in the spectrophotometer. The absorbancecharacteristics obtained are charted in FIG. 4. Water reaches a maximumabsorbance between 1400 and 1500 nanometers. The remaining componentsproduce additional changes on the long wavelength side of the main waterpeak in the 1500-1800 nanometer region in FIG. 4.

EXAMPLE 2

A polyvinyl chloride bag used for intravenous feeding (IV bag) wasfilled with sterile water, 70% dextrose injection, USP, and 10% Travasolamino acid injection, which are typical parenteral nutrients. Thesecomponents formed an optically clear solution. Utilizing the apparatusshown in FIG. 1, spectral data were attained with a germanium detectorfound in a spectrophotometer distributed by Guided Wave, Inc. under thedesignation model 200. A pair of one meter long, 500 micron corediameter, silica-clad low-OH optical fiber and collimating lenses wereemployed with the subject detector. The IV bag was compressed to anoptical path of 15 millimeters. Distinguishing characteristics wereuncovered in the compounds within the I.V. bag in the 800 to 1100nanometer region of an electromagnetic source of radiation. Referenceanalysis was also performed on an empty I.V. bag. FIG. 5 represents theresults of this analysis.

EXAMPLE 3

The parenteral compounds of Examples 1 and 2 were placed in an I.V. bagwith the addition of a common 20% Intralipid intravenous fat emulsion(I.V. fat emulsion). The final mixture of nutrients included fatcompounds occupying less than 50% of the volume of the I.V. bag mixture.FIG. 6 shows that, in spite of the light scattering characteristics ofthe milky solution found in the IV bag containing the fat compounds,transmission may still be performed, through 1-2 millimeters of anoptical path of the bag. In other words, the bag shown in FIG. 6represents a squeezing of the bag to a smaller optical path, (1.5 to 2millimeters) than the optical path represented in FIG. 5. It isestimated that 95% of the light passed through the bag in this Examplewas scattered and lost: through the first millimeter of the opticalpath. Various mixtures of 70% dextrose injection USP, 20% IntralipidI.V. fat emulsion, 10% Travasol, and water are employed and areidentified on FIG. 6. The absorbance characteristics are clearlyidentifiable for each mixture in which changes in the intensity of thewater peak near 1450 nm, effects due to amino acids and dextrose in the1500-1700 nm region, and contribution from lipid near 1200 m areidentifiable. As will be shown from diffuse reflectance spectral datahereinafter in Example 4, these features can be used to performquantitative analysis of the mixtures in the bag.

EXAMPLE 4

The apparatus shown in FIG. 3 was employed to conduct diffusereflectant/transmittance measurements through I.V. bags constructed ofpolyvinyl chloride (PVC) filled with mixtures of parenteral nutrients.The mixtures were composed of 20% Intralipid I.V. fat emulsion, 10%Travasol (amino acid injection solution), 70% dextrose injectionsolution, and sterile water. Nutrients were measured volumetrically witha graduated cylinder mixed, and placed in one (1) liter PVC I.V. bags.The device depicted in FIG. 3 was set to provide an optical path,excluding the thickness of the I.V. bag material, of about 15millimeters through the solution in the filled I.V. bag. The set screwspacer means 12, FIG. 1, was employed to compress the bag to thisparticular optical path setting. Since these mixtures all containedlipid and hence, scattered light suitable for diffuse reflectancemeasurements, the space set for the optical path was not critical to themeasurement. A spectrophotometer was employed, similar to thespectrophotometer utilized in Example 1 using an InGaAs detector. Thesource of light was a tungsten lamp. The light was delivered through a 6mm dia. hole in a white Spectralon block available from Labsphere, Inc.,North Sutton, N.H. from a 20 watt tungsten source. This block wasattached to the stationary fence 70 in FIG. 3. A bundle of 10 individualfibers of the type described in Example 1 were cemented into a smallmetal fitting and inserted through the Spectralon block at 30 degrees tothe hole containing the tungsten light source. The end of the fiberbundle fitting was coincident with the end of the block in contact withthe IV bag. Near infrared spectra were collected between 1100 and 1650nanometers. FIG. 7 depicts the results obtained where the variousmixtures used were clearly recognizable, with the exception of the 75:25Travasol and lipid mixture, which, generally, is only slightly differentfrom the 75:25 water and lipid mixture.

The spectral differences shown in FIG. 7 can be quantified with thecommonly used method of Principal Component Analysis (PCA). PCA isessentially a pattern recognition procedure that can assign one numberto the entire spectrum employed in the analysis. PCA is accomplished byanalyzing all spectral data of all samples in determining the linearcombination of data that explains the largest variation of spectralinformation. A different linear combination is next determined thatshows the next largest variation in the spectral data. The linearcombinations are determined in this way. Each linear combination isreferred to as a FACTOR which provides co-efficient that multiply thedata at each wavelength. The product of this multiplication is summed todetermine one number which is referred to as a SCORE. Thus, by plottingSCORES from FACTOR I against those from FACTOR II, samples can bedistinguished or identified. In mathematical terms, FACTORS are a set oforthogonal eigenvectors whose lengths represent the percentage ofvariation in spectral data. SCORES are obtained by multiplying theelements of each eigenvector, referred to as a LOADING (each of which isa co-efficient for the spectral data at a specific wavelength) times theabsorbance at that wavelength, and summing the results. Essentially,each sample is projected on each eigenvector and the distance from theorigin i.e., the intersection of all eigenvectors is thus measured.Other mathematical methods exist for the purposes of identification ofdata, including the computation of direction cosines, factor analysis,and cluster analysis. Referring to FIG. 8, a PCA plot is illustratedusing SCORES from the first two FACTORS of the diffuse reflectance datafrom the samples presented in FIG. 7. Table 1 herein represents thevolume fraction of the nutrients employed in the preparation of FIG. 8:

                  TABLE I    ______________________________________    SAM-  10%        STERILE   70% DEX- 20% IN-    PLE   TRAVASOL   WATER     TROSE    TRALIPID    ______________________________________    1                          0.50     0.50    2     0.50                          0.50    3                0.50               0.50    4                          0.85     0.15    5     0.85                          0.15    6                0.85               0.15    7                          0.75     0.25    8                          0.75     0.25    9     0.75                          0.25    10    0.75                          0.25    11               0.75               0.25    12               0.75               0.25    13    0.25       0.25      0.25     0.25    14    0.25       0.25      0.25     0.25    ______________________________________

These two factors account for 97% of the spectral variation among all ofthe samples, each identified by a sample number with a circle around thesame. The 70% dextrose injection USP, water, and 10% Travasol amino acidinjection components are clearly distinguished by the solid lines ofFIG. 8. The 20% intralipid fat emulsion content is also clearly shown bythe three dashed lines representing 15%, 25%, and 50% intralipid. Thesolid Travasol and water lines lie closer to one another, but aresignificantly spaced from the dextrose line in FIG. 8. Such arelationship corresponds to spectral data in which water and Travasolare more similar to each other than dextrose. Repeated measurements onthe same IV bag showed reasonable reproductibility, i.e., samples 7 and8 and samples 11 and 12 of FIG. 8.

Partial-Least Squares (PLS) method was also employed in the diffusereflectance method for the samples shown in FIG. 8. The results of thismethod are shown in FIGS. 9-10 of the present invention. Partial-LeastSquares (PLS) multivariate procedure is commonly used to determinechemical or physical property information from spectral data. Computerprograms such as UNSCRAMBLER are available from Camo of Norway.SPECTRACALC, and GRAMS/386 are available from Galactic Industries, Inc.,of Salem, N.H. Pirouette is available from Infometrics of Redmond, Wash.GRAMS/386 was used in the present analysis with a personal computer. PLSincorporates the benefits of PCA and attempts to provide a model of thedata with as few a number of FACTORS as is needed. A six FACTOR PLSmodel of the diffuse reflectance data of Table I represents a strongindication that mixtures in IV bags can be analyzed non-invasively.FIGS. 9 and 10 show predictions of 70% dextrose injection and 20%intralipid IV fat emulsion.

PLS analysis of the one millimeter optical path using transmissionthrough cuvettes, shown in FIG. 4 for samples without fat emulsion, alsoproduced excellent quantitative results. The prediction for 70% dextroseinjection USP in the mixture from a five FACTOR PLS model as presentedin FIG. 11. The standard error of calibration for the sample set was 5%.The PLS, model in FIG. 11 utilized all spectral information from allsamples as seen in FIG. 4.

Since it is often desirable to use a simple system comprising only a fewwave lengths for quantitative analysis, a multi linear Regression Method(MLR) can also be used to predict physical properties of liquids andsolids and analyze mixtures from near infrared spectra. MLR wasperformed on the one millimeter transmission spectra shown in FIG. 4.The result in calibration are presented in FIGS. 12, 13, and 14, for 70%dextrose injection USP, sterile water, and 10% Travasol amino acidinjection, respectively. The data were generated by employing 2, 3, and5 wavelengths between 1100 and 1800 nanometers, respectively. This dataare shown in Table 2 as follows:

                  TABLE II    ______________________________________    70%                         10%    DEXTROSE        WATER       TRAVASOL    SAMPLE  ACT.    PRED.   ACT.  PRED. ACT.  PRED.    ______________________________________    1       0.000   0.007   0.000 0.014 1.000 1.003    2       0.000   -0.005  1.000 0.977 0.000 0.072    3       1.000   0.986   0.000 -0.041                                        0.000 -0.061    4       0.000   0.008   0.500 0.468 0.500 0.475    5       0.500   0.522   0.500 0.517 0.000 -0.063    6       0.500   0.489   0.000 0.038 0.500 0.524    7       0.333   0.344   0.333 0.310 0.333 0.307    8       0.667   0.681   0.166 0.128 0.166 0.241    9       0.166   0.156   0.166 0.198 0.667 0.675    10      0.166   0.162   0.667 0.653 0.167 0.149    11      0.700   0.697   0.300 0.306 0.000 0.052    12      0.250   0.240   0.500 0.488 0.250 0.219    13      0.300   0.308   0.700 0.747 0.000 0.057    14      0.400   0.399   0.200 0.209 0.400 0.352    15      0.000   -0.007  0.300 0.320 0.700 0.683    ______________________________________    Wave-    length,    nm    Coeff.   Waveln.  Coeff.  Waveln.                                           Coeff.    ______________________________________    1566  16.21    1528     3.5355  1533   -51.3572    1716  -5.3741  1716     -104.7859                                    1778   56.0781    Offset          -4.9432  1744     98.6863 1287   194.9018    Mult. 0.99378  Offset   -3.4804 1193   -668.3302    R              Mult. R  0.99521 1194   455.3483    SEC   0.0347   SEC      0.0306  Offset 9.8891                                    Mult.R 0.98888                                    SEC    0.0548    ______________________________________

As may be observed, wavelengths of 1566 and 1716 nanometers wereemployed for dextrose. The wavelengths employed for water and Travasolare also shown on Table 2. The indication is that a simpler and lessexpensive system having several discrete detectors, each covered by anarrow wavelength filter or a device having means to switch betweenseveral discrete wavelengths, could be built to quantitatively predictthe composition of mixtures as these shown in FIG. 4.

A stepwise multiple linear regression program was also used to determinea small set of wavelengths which could be used to predict the intralipidand 70% dextrose mixture in IV bags filled with the samples identifiedin Table II, analyzed by the embodiment of 10A of FIG. 1(transmittance). The optical path was set to a distance of approximately1.6 mm. Actual versus predicted values were plotted as shown on FIG. 15.It should be noted that a perfect calibration would plot on the diagonalline found in FIG. 15. Three (3) and five (5) wavelengths were used toproduce excellent fits with standard errors of prediction of 2.1 and3.7% for the 20% intralipid component and the 70% dextrose component inthe mixture, respectively. The three (3) wavelengths used for the 20%intralipid were 1606, 1536, and 1532 nanometers which are listed indecreasing order of importance. Similarly, the five (5) lengths employedfor the 70% dextrose were 1414, 1610, 1212, 1424, and 1200 nanometers,also listed in order of importance. Each mathematical solution alsoincluded a constant term.

What is claimed is:
 1. An apparatus for measuring a component in aliquid medium within the chamber of a flexible translucent containerformed by a wall portion, comprising:a. spacer means for sequentiallydetermining a plurality of optical paths across the container wallportion and chamber, and the flexible translucent container wall portionalone, said spacer means including a passage for electromagneticradiation; and b. a source of electromagnetic radiation capable ofdirecting electromagnetic radiation through said spacer means passage,through the wall portion of the container, and along any of saiddetermined optical paths, said source of electromagnetic radiation beingcapable of interaction with a component in the bag chamber and the wallportion of the bag; and c. detector means for analyzing saidelectromagnetic radiation after interaction with the components in theflexible translucent container chamber and the wall portion of the bag.2. The apparatus of claim 1 in which said spacer means includes a pairof elements placed in opposition to one another, at least one of saidelements including a passage for electromagnetic radiation to the wallportion of the bag.
 3. The apparatus of claim 2 in which additionallycomprises adjustment means for establishing the distance between saidpair of elements.
 4. The apparatus of claim 3 in which said adjustmentmeans includes a threaded member spanning said pair of elements, saidthreaded member threadingly engaging one of said elements to effectmovement said one of said elements thereby, and a guide for confiningmovement of said one of said elements to a predefined direction.
 5. Theapparatus of claim 4 in which said guide includes a pair of elongatedelements extending between said pair of elements.
 6. The apparatus ofclaim 1 which additionally includes a fiber optic conduit fortransporting electromagnetic radiation from said source ofelectromagnetic radiation to said spacer means passage.
 7. The apparatusof claim 6 which additionally includes a fiber optic conduit fortransporting electromagnetic radiation from said spacer means to saiddetector means.
 8. The apparatus of claim 2 which additionally comprisesa reflector located at one of said pair of elements, said reflectorbeing located to reflect electromagnetic radiation, passed through thechamber of the flexible translucent bag back through the chamber of theflexible translucent bag.
 9. The apparatus of claim 1 in which saidsource of electromagnetic radiation emanates electromagnetic radiationin the near-infrared region of the electromagnetic spectrum.
 10. Theapparatus of claim 1 which additionally includes at least one wavelengthfilter placed between said source of electromagnetic radiation and saiddetector means.
 11. The apparatus of 10 which additionally includes alens placed between said source of electromagnetic radiation and saiddetector means.
 12. A method of analyzing components in a liquid mediumwithin the chamber of a flexible bag comprising the steps of:a. placingthe bag in spacer means for determining the optical path across the bagchamber, said spacer means including a passage for electromagneticradiation; b. directing electromagnetic radiation from a source ofelectromagnetic radiation to the components in said bag chamber forinteraction therewith; and c. analyzing said electromagnetic radiationwith detector means after interaction of said electromagnetic radiationwith the components in the bag chamber.
 13. The method of claim 12 inwhich said step of analyzing said electromagnetic radiation furtherincludes the step of analyzing electromagnetic radiation transmittedthrough said components in the bag chamber.
 14. The method of claim 12in which said step of analyzing said electromagnetic radiation furtherincludes the step of analyzing electromagnetic radiation reflected fromsaid components in the flexible bag.
 15. The method of claim 12 in whichsaid step of analyzing said electromagnetic radiation further includesthe step of analyzing electromagnetic radiation transmitted through andreflected back through components in the bag chamber.
 16. The method ofclaim 12 which further comprises the step of passing electromagneticradiation through the flexible bag alone in order to obtain a referencespectrum.
 17. The method of claim 16 which further comprises the step ofexpelling the liquid medium from the flexible bag prior to said step ofpassing electromagnetic radiation through the flexible bag alone. 18.The method of claim 16 in which said step of placing the bag in spacermeans for determining the optical path across the bag chamber is a firstoptical path and further includes the step of placing the bag in saidspacer means for determining a second optical path across the bagchamber; directing electromagnetic radiation to the components in saidchamber for interaction therewith; and analyzing said electromagneticradiation with said detector means after interaction of saidelectromagnetic radiation with the components in the bag chamber. 19.The method of claim 12 in which said components are parenteral andenteral nutrients.
 20. An apparatus for detecting light scatteringcomponents in a liquid medium within the chamber of a flexibletranslucent bag formed by a wall portion, comprising:a. a fence element,said fence element including a passage for electromagnetic radiation tothe wall portion of the bag, said fence element further determining theoptical path across the flexible translucent bag chamber; b. a source ofelectromagnetic radiation capable of directing electromagnetic radiationthrough said fence element passage, said source of electromagneticradiation being capable of interaction with a component in the bagchamber and the wall portion of the bag; and c. detector means foranalyzing said electromagnetic radiation after interaction with thecomponents in the bag chamber and the wall portion of the bag, saiddetector means receiving said electromagnetic radiation, afterinteraction with a component in the bag chamber, through said fencepassage.
 21. An apparatus for non-invasively identifying components in aliquid medium within an interior of a flexible bag, the apparatuscomprising:a. a source of electromagnetic radiation capable of directingelectromagnetic radiation into the interior of the bag, the source ofelectromagnetic radiation capable of interaction with the components inthe bag chamber and the bag; b. means for defining the optical path thatthe electromagnetic radiation travels across the interior of the bag; c.optical detector means located outside the bag receiving theelectromagnetic radiation after interaction with the components in thebag chamber interior and the wall portion of the bag, and providing asignal indicative thereof; and d. means for analyzing the signal toidentify the components of the liquid medium in the bag.